title: Regulation of proteasome activity in activated human platelets.
abstract: Ubiquitin-proteasome system has emerged a central player in regulation of diverse cellular processes. However, relevance of proteasome activity in platelets, which are terminally differentiated enucleate cells, is not clear. In this report we show that activation of platelets with physiological agonists was associated with 7-10 -fold rise in proteasomal activity. Elevation of cytosolic calcium with A23187 or thapsigargin resulted in significant increase in enzymatic activity, while treatment with intracellular calcium chelator or inhibitor of inositol trisphosphate receptor attenuated proteasomal enzymes in collagen-stimulated platelets. Specific inhibitors of protein kinase C as well as calpain, too, downregulated proteasome function. To conclude, proteasomal enzymatic activity in platelets is regulated by cytosolic calcium through Ca(2+)-dependent downstream effectors like calpain and protein kinase C.
authors.affiliation: Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Manasa K
authors.initials: MK
authors.lastname: Nayak
authors.forename: Kailash
authors.initials: K
authors.lastname: Kumar
authors.forename: Debabrata
authors.initials: D
authors.lastname: Dash
mesh_terms: D001792:Blood Platelets / Q000201:enzymology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D002614:Chelating Agents; D053496:Inositol 1,4,5-Trisphosphate Receptors; D000001:Calcimycin; D019284:Thapsigargin; D011493:Protein Kinase C; D002154:Calpain; D046988:Proteasome Endopeptidase Complex; D002118:Calcium